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Publications

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Research Abstract

A versatile nanocarrier for in vivo tumor-targeted drug delivery: We have developed a novel biocompatible amphiphilic linear-dendritic co-polymer (named telodendrimer), using biocompatible PEG and bio-sourced cholic acid and lysine as building blocks. It can self-assemble into micelles in aqueous solution for the encapsulation of hydrophobic drugs, such as paclitaxel (PTX) and doxorubicin (DOX) with superior drug loading capacity and stability, which is due to the unique facial amphiphilicity of cholic acid. The stepwise peptide chemistry allow for the modular design of telodendrimers and precise control of the density and sites of the functional group. The Multi-functionality feature of telodendrimers allows for the decoration of micelle nanoparticles with targeting molecules, imaging probes, and reactive functional groups for micelle crosslinking. This nanotherapeutic is able to target tumor in animal models effectively via both passive enhanced permeability and retention (EPR) effect and active tumor targeting (via ligand decoration). As shown in our recent publications, PTX and DOX loaded in this nanocarrier have exhibited superior anticancer effects in animal models over their clinical formulations. Currently, our research interests are focusing the de novo design of nanocarrier via the aid of computational approaches (MD simulation, molecular docking) and systematic evaluation and optimization of nanocarriers via combinatorial synthesis for the efficient delivery of various hydrophobic anticancer drugs. In addition, our recent studies demonstrated that telodendrimers could also self-assemble into core-inversed micelles (CIMs) selectively in some apolar solvents. CIMs have a hydrophilic core for hydrophilic molecule encapsulation. CIMs can be crosslinked and easily extracted into aqueous solution with payloads encapsulated for intracellular delivery of hydrophilic drugs, such as small molecules, peptides and proteins. Furthermore, positively charged amines can be introduced into the adjacent sites of telodendrimer to form micelles with the segregated domains for the co-delivery of gene molecules and hydrophobic drugs for the combination cancer therapy.

............This work was highlighted as the Most Important Paper (MIP) in the Inside Back Cover of the Week in Angewandte Chemie International Edition2012, 51(12), 3027. This research was highlighted as a short news story in Therapeutic Delivery 2012, 3(3), 303-306.................................................................